6-(Perfluoroalkyl)uracil compounds are useful as herbicidal agents and methods for their preparation are known in the art. 6-(Perfluoroalkyl)uracil compounds may be prepared by reacting 2-(N,N-disubstituted)amino-4-(perfluoroalkyl)-1,3-oxazin-6-one compounds with amine compounds.
Bull. Soc. Chem. Belg., 101(4), pages 313-321 (1992) discloses that 2-(N,N-dialkyl)amino-4-(trifluoromethyl)-1,3-oxazin-6-one compounds are prepared by reacting ethyl 3-amino-4,4,4-trifluorocrotonate with phosgene iminium chloride compounds. However, this method is not entirely satisfactory for the preparation of 2-(N,N-disubstituted)amino-4-(perfluoroalkyl)-1,3-oxazin-6-one compounds because the required phosgene iminium chloride compounds are difficult to handle and relatively expensive. Accordingly, a need exists in the art for an improved process for the preparation of 2-(N,N-disubstituted)amino-4-(perfluoroalkyl)-1,3-oxazin-6-one compounds which avoids the use of phosgene iminium chloride compounds.
It is, therefore, an object of the present invention to provide improved processes for the preparation of 2-(N,N-disubstituted)amino-4-(perfluoroalkyl)-1,3-oxazin-6-one compounds.
It is also an object of the present invention to provide intermediate compounds which are useful in the preparation of 2-(N,N-disubstituted)amino-4-(perfluoroalkyl)-1,3-oxazin-6-one compounds.
It is a further object of the present invention to provide an improved process for the preparation of 6-(perfluoroalkyl)uracil compounds.
Other objects and advantages of the present invention will be apparent to those skilled in the art from the description below and the appended claims.
The present invention provides a new process for the preparation of 2-(N,N-disubstituted)amino-4-(perfluoroalkyl)-1,3-oxazin-6-one compounds having the structural formula I 
wherein
Z and Z1 are each independently C1-C8alkyl or Z and Z1 may be taken together with the atom to which they are attached to form a 4- to 7-membered ring wherein ZZ1 is represented by xe2x80x94(CH2)2O(CH2)2xe2x80x94 or xe2x80x94(CH2)mxe2x80x94 where m is an integer of 3, 4, 5 or 6; and
n is an integer of 1, 2, 3, 4, 5 or 6,
which comprises:
(a) reacting a xcex2-amino-xcex2-(perfluoroalkyl)acrylate compound having the structural formula II 
wherein n is as described above, and Z2 is C1-C6alkyl or benzyl optionally substituted on the phenyl ring with any combination of from one to three halogen, C1-C4alkyl or C1-C4haloalkyl groups, with a base and a carbamoyl chloride compound having the structural formula III 
wherein Z and Z1 are as described above to form a urea compound having the structural formula IV 
(b) reacting the formula IV urea with a phosphorous pentahalide or oxalyl halide.
The present invention further provides a process for the preparation of 6-(perfluoroalkyl)uracil compounds having the structural formula V 
wherein
n is an integer of 1, 2, 3, 4, 5 or 6;
Z3 is hydrogen or C1-C6alkyl; and
Q is a C1-C6alkyl group or an optionally substituted phenyl, benzyl, heteroaryl or methyleneheteroaryl group,
which process comprises:
(a) reacting a urea compound having the structural formula IV 
wherein
Z and Z1 are each independently C1-C8alkyl or Z and Z1 may be taken together with the atom to which they are attached to form a 4- to 7-membered ring wherein
ZZ1 is represented by xe2x80x94(CH2)2O(CH2)2xe2x80x94 or xe2x80x94(CH2)mxe2x80x94 where m is an integer of 3, 4, 5 or 6;
Z2 is C1-C6alkyl or benzyl optionally substituted on the phenyl ring with any combination of from one to three halogen, C1-C4alkyl or C1-C4haloalkyl groups; and
n is as described above, with a phosphorous pentahalide or oxalyl chloride to form a 2-(N,N-disubstituted)amino-4-(perfluoroalkyl)-1,3-oxazin-6-one compound having the structural formula I 
(b) reacting the 2-(N,N-disubstituted)amino-4-(perfluoroalkyl)-1,3-oxazin-6-one with an amine compound having the structural formula VI
QNH2xe2x80x83xe2x80x83(VI)
wherein Q is as described above in the presence of an acid or a base to form the 6-(perfluoroalkyl)uracil compound of formula V wherein Z3 is hydrogen; and
(c) optionally alkylating the formula V compound wherein Z3 is hydrogen.
The present invention also relates to the novel urea compounds having the structural formula IV 
wherein
Z and Z1 are each independently C1-C8alkyl or Z and Z1 may be taken together with the atom to which they are attached to form a 4- to 7-membered ring wherein ZZ1 is represented by xe2x80x94(CH2)2O(CH2)2xe2x80x94 or xe2x80x94(CH2)mxe2x80x94 where m is an integer of B, 4, 5 or 6;
n is an integer of 1, 2, 3, 4, 5 or 6; and
Z2 is C1-C6alkyl or benzyl optionally substituted on the phenyl ring with any combination of from one to three halogen, C1-C4alkyl or C1-C4haloalkyl groups.
In a preferred embodiment of the present invention, the 2-(N,N-disubstituted)amino-4-(perfluoroalkyl)-1,3-oxazin-6-one compounds of formula I are prepared by reacting a xcex2-amino-xcex2-(perfluoroalkyl)acrylate compound of formula II with a base and a carbamoyl chloride compound of formula III, preferably at a temperature ranging from about xe2x88x9220xc2x0 C. to 80xc2x0 C., more preferably from about 0xc2x0 C. to 50xc2x0 C., in the presence of a first solvent to form a urea compound of formula IV, and reacting the formula IV urea compound with a phosphorous pentahalide or oxalyl halide, preferably at a temperature ranging from about 0xc2x0 C. to 100xc2x0 C., more preferably from about 20xc2x0 C. to 50xc2x0 C., optionally in the presence of a second solvent.
The present invention also provides a process for the preparation of 2-(N,N-disubstituted)amino-4-(perfluoroalkyl)-1,3-oxazin-6-one compounds of formula I which comprises reacting a urea compound of formula IV with a phosphorous pentahalide or oxalyl chloride, preferably at a temperature ranging from about 0xc2x0 C. to 100xc2x0 C., more preferably from about 20xc2x0 C. to 50xc2x0 C., optionally in the presence of a second solvent.
Advantageously, the present invention provides improved processes for the preparation of 2-(N,N-disubstituted)amino-4-(perfluoroalkyl)-1,3-oxazin-6-one compounds which avoid the use of phosgene iminium chloride compounds.
The present invention further relates to urea compounds having the structural formula IV which are utilized in the processes of this invention 
wherein
Z and Z1 are each independently C1-C8alkyl or Z and Z1 may be taken together with the atom to which they are attached to form a 4- to 7-membered ring wherein ZZ1 is represented by xe2x80x94(CH2)2O(CH2)2xe2x80x94 or xe2x80x94(CH2)mxe2x80x94 where m is an integer of 3, 4, 5 or 6;
n is an integer of 1, 2, 3, 4, 5 or 6; and
Z2 is C1-C6alkyl or benzyl optionally substituted on the phenyl ring with any combination of from one to three halogen, C1-C4alkyl or C1-C4haloalkyl groups.
Preferred formula IV compounds are those wherein
Z and Z1 are each independently C1-C6alkyl;
Z2 is C1-C4alkyl; and
n is 1.
More preferred formula IV urea compounds of this invention are those wherein
Z and Z1 are the same and represent methyl or ethyl;
Z2 is methyl or ethyl; and
n is 1.
Representative formula IV compounds which are particularly useful in the processes of this invention include
ethyl 3-[(N,N-dimethylcarbamoyl)amino]-4,4,4-trifluorocrotonate, (Z)-;
methyl 3-[(N,N-dimethylcarbamoyl)amino]-4,4,4-trifluorocrotonate, (Z)-;
ethyl 3-[(N,N-diethylcarbamoyl)amino]-4,4,4-trifluorocrotonate, (Z)-;
methyl 3-[(N,N-diethylcarbamoyl)amino]-4,4,4-trifluorocrotonate, (Z)-;
ethyl 3-[(N-pyrrolodinecarbonyl)amino]-4,4,4-trifluorocrotonate, (Z)-; and
methyl 3-[(N-pyrrolodinecarbonyl)amino]-4,4,4-trifluorocrotonate, (Z)-, among others.
In another preferred embodiment of the present invention, the double bond in the formula II and IV compounds is predominately in the (Z)-configuration.
The product formula I compounds may be isolated by diluting the reaction mixture with water and extracting the product with a suitable extraction solvent. In the isolation procedure, conventional extraction solvents such as diethyl ether, ethyl acetate, toluene, methylene chloride, and the like, and mixtures thereof may be utilized.
Bases suitable for use in the preparation of the formula IV urea compounds include, but are not limited to, alkali metal hydrides such as sodium hydride and the like; alkali metal C1-C6alkoxides such as potassium tert-butoxide, sodium tert-butoxide and the like; alkali metal hydroxides such as potassium hydroxide, sodium hydroxide and the like; alkali metal carbonates such as sodium carbonate, potassium carbonate and the like; alkaline earth metal hydroxides such as calcium hydroxide and the like; alkaline earth metal carbonates such as calcium carbonate and the like; and lithium bases such as alkyllithiums including n-butyllithium, sec-butyllithium, tert-butyllithium, methyllithium and the like, lithium dialkylamides including lithium diisopropylamide and the like, and lithium cyclicamides including lithium tetramethylpiperidine and the like. Preferred first bases include alkali metal hydrides and alkali metal C1-C6alkoxides.
Phosphorous pentahalides suitable for use in the processes of this invention include phosphorous pentachloride, phosphorous pentabromide and phosphorous pentaiodide with phosphorous pentachloride being preferred. Oxalyl halides suitable for use in this invention include oxalyl chloride, oxalyl bromide and oxalyl iodide, with oxalyl chloride being preferred.
First solvents useful in this invention include, but are not limited to, carboxylic acid amides such as N,N-dimethylformamide, N,N-dimethylacetamide and the like; ethers such as diethyl ether, tetrahydrofuran, dioxane, 1,2-dimethoxyethane and the like; nitriles such as acetonitrile, propionitrile and the like; dialkyl sulfoxides such as dimethyl sulfoxide and the like; and mixtures thereof. A preferred first solvent is N,N-dimethylformamide.
Second solvents suitable for use in the present invention include, but are not limited to, phosphorous oxyhalides such as phosphorous oxychloride and the like; aromatic hydrocarbons such as toluene, benzene, xylenes, mesitylene and the like; halogenated aromatic hydrocarbons such as chlorobenzene, fluorobenzene and the like; carboxylic acid amides such as N,N-dimethylformamide, N,N-dimethylacetamide and the like; aliphatic hydrocarbons such as pentane, hexane, heptane and the like; halogenated aliphatic hydrocarbons such as methylene chloride, chloroform, carbon tetrachloride, 1,2-dichloroethane and the like; and mixtures thereof. A preferred second solvent is phosphorous oxychloride.
Preferred formula I compounds which may be prepared by the processes of this invention are those wherein
Z and Z1 are each independently C1-C6alkyl; and
n is 1.
The processes of the present invention are also preferably used for the preparation of formula I compounds wherein
Z and Z1 are the same and represent methyl or ethyl; and
n is 1.
The 2-(N,N-disubstituted)amino-4-(perfluoroalkyl)-1,3-oxazin-6-one compounds of formula I are useful for the preparation of herbicidal 6-(perfluoroalkyl)uracil compounds having the structural formula V 
wherein
n is an integer of 1, 2, 3, 4, 5 or 6;
Z3 is hydrogen or C1-C6alkyl; and
Q is a C1-C6alkyl group or an optionally substituted phenyl, benzyl, heteroaryl or methylenehetero-aryl group.
Advantageously, formula V 6-(perfluoroalkyl)uracil compounds may be prepared by a process which comprises:
(a) reacting a urea compound having the structural formula IV 
wherein
Z and Z1 are each independently C1-C8alkyl or Z and Z1 may be taken together with the atom to which they are attached to form a 4- to 7-membered ring wherein
ZZ1 is represented by xe2x80x94(CH2)2O(CH2)2xe2x80x94 or xe2x80x94(CH2)mxe2x80x94 where m is an integer of 3, 4, 5 or 6;
Z2 is C1-C6alkyl or benzyl optionally substituted on the phenyl ring with any combination of from one to three halogen, C1-C4alkyl or C1-C4haloalkyl groups; and
n is as described above, with a phosphorous pentahalide or oxalyl halide to form a 2-(N,N-disubstituted)amino-4-(perfluoroalkyl)-1,3-oxazin-6-one compound having the structural formula I 
(b) reacting the 2-(N,N-disubstituted)amino-4-(perfluoroalkyl)-1,3-oxazin-6-one with an amine compound having the structural formula VI
xe2x80x83QNH2xe2x80x83xe2x80x83(VI)
wherein Q is as described above in the presence of an acid or a base to form the 6-(perfluoroalkyl)uracil compound of formula V wherein Z3 is hydrogen; and
(c) optionally alkylating the formula V compound wherein Z3 is hydrogen.
Acids suitable for use in the preparation of the formula V compounds include organic acids including, but not limited to, C1-C6alkanoic acids such as formic acid, acetic acid, propionic acid and the like; and mineral acids including, but not limited to, hydrochloric acid, sulfuric acid, phosphoric acid and the like. A preferred acid is acetic acid.
Bases suitable for use in the preparation of the formula V compounds include, but are not limited to, tri(C1-C6alkyl)amines such as trimethylamine, triethylamine, tripropylamine, tributylamine, diisopropylethylamine and the like; heterocyclic tertiary amines such as 1,8-diazazbicyclo[5.4.0]undec-7-ene (DBU), 1,5-diazabicyclo[4.3.0]non-5-ene (DBN), 1,4-diazabicyclo[2.2.2]octane, pyridine, substituted pyridines, quinoline, substituted quinolines and the like; and alkali metal C1-C6alkoxides such as potassium tert-butoxide, sodium tert-butoxide and the like. Preferred second bases include 1,8-diazabicyclo[5.4.0]-undec-7-ene and 1,5-diazabicyclo[4.3.0]non-5-ene.
In a preferred embodiment of the present invention, the 2-(N,N-disubstituted)amino-4-(perfluoroalkyl)-1,3-oxazin-6-one is reacted with the amine and the acid, preferably at a temperature ranging from about 20xc2x0 C. to 150xc2x0 C., in the presence of a third solvent. Third solvents suitable for use in this reaction include, but are not limited to, carboxylic acid amides such as N,N-dimethylformamide, N,N-dimethylacetamide and the like; dialkyl sulfoxides such as dimethyl sulfoxide and the like; aromatic hydrocarbons such as toluene, benzene, xylenes, mesitylene and the like; halogenated aromatic hydrocarbons such as chlorobenzene, fluorobenzene and the like; aliphatic hydrocarbons such as pentane, hexane, heptane and the like; halogenated aliphatic hydrocarbons such as methylene chlorine, chloroform, carbon tetrachloride, 1,2-dichloroethane and the like; alkanoic acids such as formic acid, acetic acid, propionic acid and the like; ketones such as acetone, methyl ethyl ketone and the like; ethers such as diethyl ether, tetrahydrofuran, dioxane, 1,2-dimethoxyrethane and the like; nitriles such as acetonitrile, propionitrile and the like; and water; and mixtures thereof.
Alkylation procedures suitable for use in this invention include conventional procedures known in the art. In a preferred embodiment of this invention, the alkylation procedure comprises reacting the formula V compound wherein Z3 is hydrogen with an alkyl halide having the structural formula VII or a dialkylsulfate ester having the structural formula VIII 
wherein X is chlorine, bromine or iodine, and Z3 is C1-C6alkyl in the presence of a base.
Bases suitable for use in the alkylation procedures of this invention include conventional bases known in the art including, but not limited to, alkali metal hydrides such as sodium hydride and the like; alkali metal C1-C6alkoxides such as potassium tert-butoxide, sodium tert-butoxide and the like; alkali metal hydroxides such as potassium hydroxide, sodium hydroxide and the like; alkali metal carbonates such as sodium carbonate, potassium carbonate and the like; alkaline earth metal hydroxides such as calcium hydroxide and the like; and alkaline earth metal carbonates such as calcium carbonate and the like.
Preferred formula V compounds which may be prepared by the process of the present invention are those wherein
n is 1;
Z3 is hydrogen or C1-C4alkyl;
Q is 
G is CH2 or a bond;
G1 is CX5 or N;
G2 is CX4 or N;
X1 is hydrogen, halogen or a C1-C6alkyl group optionally substituted with one epoxy group,
X2 is hydrogen, halogen NRR1, CO2R2, C(O)R3, OR4, SO2R5, SO2NR6R7, C(R8) (OR9)2, C(R10)xe2x95x90NOR11, C(R12)xe2x95x90C(R13)xe2x80x94C(OR14)xe2x95x90NOR15, CH2Oxe2x80x94NCO2R16,
1,3-dioxolane optionally substituted with one C1-C6alkoxy group or one or two C1-C4alkyl groups,
1,3-dioxolinone optionally substituted with one C1-C6alkoxy group or one or two C1-C4alkyl groups, or
C1-C4alkyl optionally substituted with one CO2R2 group and one halogen atom, and
X3 is hydrogen, halogen, C1-C4haloalkyl, CO2R17, cyano, C1-C4haloalkoxy, OR18 or C1-C4alkyl, or
when X1 and X2 are taken together with the atoms to which they are attached, they may form a five- or six-membered ring wherein X1X2 or X2X1 is represented by:
xe2x80x94OC(R20)(R21)Oxe2x80x94, 13 CH2S(O)pN (R22)xe2x80x94, xe2x80x94SC(R23)xe2x95x90Nxe2x80x94, xe2x80x94CHxe2x95x90CHxe2x80x94CH(R11)Oxe2x80x94, xe2x80x94OC(O)Nxe2x80x94, xe2x80x94SC(R24)xe2x95x90Nxe2x80x94, xe2x80x94ON(R25)C(O)xe2x80x94,
xe2x80x94OC(CO2R26)xe2x95x90C(R27)xe2x80x94, xe2x80x94NC(R28)xe2x95x90C(SR29)xe2x80x94, xe2x80x94CHxe2x95x90C(CO2R30)Oxe2x80x94,
xe2x80x94CH2CH(R31)Oxe2x80x94 or xe2x80x94OC(R32)(R33)C(O)xe2x80x94, or
when X2 and X3 are taken together with the atoms to which they are attached, they may form a five- or six-membered ring wherein X2X3 or X3X2 is represented by:
xe2x80x94NC(R34)xe2x95x90NC(S)xe2x80x94, xe2x80x94N(R35)Nxe2x95x90C(R36)xe2x80x94, xe2x80x94N(R37)C(R38)xe2x95x90Nxe2x80x94,
xe2x80x94N(R38)C(O)CH2Oxe2x80x94, xe2x80x94N(R39)C(O)CHxe2x95x90CHxe2x80x94, xe2x80x94Sxe2x80x94Nxe2x95x90C(R40)xe2x80x94,
xe2x80x94Oxe2x80x94Nxe2x95x90C(R41)xe2x80x94, xe2x80x94Nxe2x95x90Nxe2x80x94N(R42)xe2x80x94, xe2x80x94C(R43)(R44)C(O)N(R45)xe2x80x94 or
xe2x80x94N(R46)C(O)C(R47)(R48)xe2x80x94;
X4 is hydrogen, halogen or OR19;
X5 is hydrogen or halogen;
R, R56, R64, R69, R70, R77 and R91 are each independently hydrogen, SO2R49, C1-C4alkyl, C3-C7cycloalkyl, C3-C6alkenyl, C3-C6alkynyl, phenyl or benzyl;
R1 is hydrogen, SO2R50, C(O)R51, amino or C1-C4alkyl optionally substituted with CO2R52 or C(O)R53;
R2, R16, R17, R26, R30, R68, R75, R76, R82 and R88 are each independently hydrogen, C1-C8haloalkyl, C3-C8alkenyl, C3-C6alkynyl, phenyl, benzyl, furfuryl, pyridyl, thienyl,
C1-C8alkyl optionally substituted with CO2R54, morpholine or C(O)R55, or
an alkali metal, an alkaline earth metal, ammonium or organic ammonium cation;
R3, R66, R67, R81, R85 and R89 are each independently hydrogen,
C1-C6alkyl, C3-C6alkenyl, C3-C6alkynyl, NR56R57, phenyl or benzyl;
R4, R18, R19 and R65 are each independently hydrogen,
C1-C6alkyl, C3-C6alkenyl, C3-C6alkynyl, C1-C4haloalkyl, C(O)R58, C(S)R59 or benzyl;
R5 and R72 are each independently C1-C6alkyl, C1-C6haloalkyl,
NR60R61, imidazole or indazole;
R6, R11, R12, R14, R15, R20, R21, R22, R25, R28, R29, R31, R32, R33, R35, R45, R46, R63 and R80 are each independently hydrogen or C1-C4alkyl;
R7 is hydrogen, C3-C6alkenyl, C3-C6alkynyl, benzyl, or
C1-C4alkyl optionally substituted with cyano or C(O)R62;
R8 and R27 are each independently hydrogen, C1-C4alkyl or C1-C4alkoxy;
R9 and R90 are each independently C1-C6alkyl;
R10 is hydrogen, C1-C6alkyl, phenyl or benzyl;
R13, R24 and R36 are each independently hydrogen, C1-C6alkyl or halogen;
R23 is hydrogen or NR63R64;
R34 is hydrogen, C1-C4alkyl or C1-C4haloalkyl;
R37 is hydrogen, C1-C4alkyl or C2-C8alkoxyalkyl;
R38 and R39 are each independently hydrogen, C1-C4alkyl, C1-C4haloalkyl, C3-C6alkenyl or C3-C6alkynyl;
R40, R41 and R42 are each independently hydrogen, halogen, cyano, OR65, C(O)R66, C(S)R67, CO2R68, C(xe2x95x90NOR69),
a C1-C8alkyl, C3-C7cycloalkyl, C2-C8alkenyl or C2-C8alkynyl group, wherein each group is optionally substituted with any combination of one to six halogen atoms, one to three C1-C10-alkoxy groups, one or two C1-C6haloalkoxy groups, one or two NR70R71 groups, one or two S(O)qR72 groups, one or two cyano groups, one or two C3-C7cycloalkyl groups, one OSO2R73 group, one or two C(O)R74 groups, one or two CO2R75 groups, one or two C(O)SR76 groups, one or two C(O)NR77R78 groups, one to three OR79 groups, one or two P(O)(OR53)2 groups, one 1,3-dioxolane optionally subsituted with one to three C1-C4alkyl groups, or one 1,3-dioxane optionally substituted with one to three C1-C4alkyl groups, or
phenyl or benzyl optionally substituted with any combination or of to three halogen atoms, one to three C1-C6alkyl groups, one to three C1-C6alkoxy groups, one C3-C7cycloalkyl group, one C1-C4haloalkyl a group, one C1-C4alkylthio group, one cyano group, one nitro group, one C(O)R81 group, one CO2R32 group, one OR83 group, one SR84 group, one C1-C8alkoxymethyl group, one hydroxymethyl group, one C3-C8alkenyloxymethyl group, or one C1-C8haloalkoxymethyl group;
R43, R44, R47 and R48 are each independently hydrogen,
C1-C4alkyl, C1-C4haloalkyl, C3-C6alkenyl, C3-C6alkynyl or C3-C7cycloalkyl, or R43 and R44 or R47 and R48 may be taken together with the atom to which they are attached to form a C3-C7cycloalkyl group;
R49, R50 and R86 are each independently C1-C6alkyl, NR93R94, C1-C4haloakyl, C3-C6alkenyl, C3-C6alkynyl or benzyl;
R51, R52, R53, R54, R55, R57, R58, R59, R60, R61, R62, R71, R73, R74, R78, R87 and R92 are each independently hydrogen,
C1-C6alkyl, C3-C7cycloalkyl, C1-C6haloalkyl,
C3-C6alkenyl, C3-C6alkynyl, phenyl or benzyl;
R79, R83 and R84 are each independently hydrogen,
C(O)R85, SO2R86, C1-C6haloalkyl, C2-C6alkenyl,
C5-C8cycloalkenyl, C2-C6alkynyl, phenyl, benzyl, or
C1-C10alkyl optionally substituted with one hydroxyl, benzyloxy, OC(O)R87, C1-C6alkoxy, CO2R88, C(O)R89, C(OR90)2, C(O)NR91R92 or cyano group;
R93 and R94 are each independently hydrogen, C1-C4haloalkyl,
C2-C6alkenyl, C3-C8cycloalkyl,
C1-C8alkyl optionally substituted with one or two C1-C4alkoxy groups or one cyanoalkyl group, or
benzyl or phenyl opzionally substituted with any combination of one to three halogen atoms, one to three C1-C4alkyl groups, one to three C1-C4haloalkyl groups, one to three C1-C4alkoxy groups, one to three C1-C4haloalkoxy groups, one cyano group or one nitro group, and
when R93 and R94 are taken together with the atom to which they are attached, they form a 5- to 12-membered monocyclic or fused bicyclic, heterocyclic ring optionally substituted with one or more groups independently selected from halogen, cyano, nitro, amino, hydroxyl, C2-C4alkyl, C1-C4haloalkyl,
C1-C4alkoxy, C1-C4haloalkoxy and C1-C4haloalkylsulfonyl groups; and
p and q are each independently 0, 1 or 2; and
the optical isomers, diastereomers and/or tautomers thereof.
More preferred formula V herbicidal agents which may be prepared by the process of this invention are those
wherein
n is 1;
Z3 is hydrogen or methyl;
Q is 
G is CH2 or a bond;
G1 is CX5 or N;
G2 is CX4 or N;
X1 is hydrogen, fluorine or C1-C3alkyl optionally substituted with one epoxy group;
X2 is hydrogen, halogen NRR1, CO2R2, C(O)R3, OR4, SO2R5,
SO2NR6R7, C(R8)(OR9)2, C(R10)xe2x95x90NOR11, C(R12)xe2x95x90C(R13)xe2x80x94C(OR14)xe2x95x90NOR15, CH2Oxe2x80x94NCO2R16,
1,3-dioxolane optionally substituted with one C1-C6alkoxy group or one or two C1-C4alkyl groups,
1,3-dioxolinone optionally substituted with one C1-C6alkoxy group or one or two C1-C4alkyl groups, or
C1-C4alkyl optionally substituted with one CO2R2 group and one halogen atom, and
X3 is hydrogen, halogen, C1-C4haloalkyl, CO2R17, cyano,
C1-C4haloalkoxy, OR18 or C1-C4alkyl, or
when X1 and X2 are taken together with the atoms to which they are attached, they may form a five- or six-membered ring wherein X1X2 or X2X1 is represented by:
xe2x80x94OC(R20)(R21)Oxe2x80x94, xe2x80x94CH2S(O)pN(R22)xe2x80x94, xe2x80x94SC(R23)xe2x95x90Nxe2x80x94,
xe2x80x94CHxe2x95x90CHxe2x80x94CH(R11)Oxe2x80x94, xe2x80x94OC(O)Nxe2x80x94, xe2x80x94SC(R24)xe2x95x90Nxe2x80x94, xe2x80x94ON(R25)C(O)xe2x80x94,
xe2x80x94OC(CO2R26)xe2x95x90CHxe2x80x94, xe2x80x94NC(R28)xe2x95x90C(SR29)xe2x80x94, xe2x80x94CHxe2x95x90C(CO2R30)Oxe2x80x94,
xe2x80x94CH2CH(R31)Oxe2x80x94 or xe2x80x94OC(R32)(R33)C(O)xe2x80x94, or
when X2 and X3 are taken together with the atoms to which they are attached, they may form a five- or six-membered ring wherein X2X3 or X3X2 is represented by:
xe2x80x94NC(R34)xe2x95x90NC(S)xe2x80x94, xe2x80x94N(R35)Nxe2x95x90C(R36)xe2x80x94, xe2x80x94N(R37)C(R38)xe2x95x90Nxe2x80x94,
xe2x80x94N(R38)C(O)CH2Oxe2x80x94, xe2x80x94N(R39)C(O)CHxe2x95x90CHxe2x80x94, xe2x80x94Sxe2x80x94Nxe2x95x90C(R40)xe2x80x94,
xe2x80x94Oxe2x80x94Nxe2x95x90C(R41)xe2x80x94, xe2x80x94Nxe2x95x90Nxe2x80x94N(R42)xe2x80x94, xe2x80x94C(R43)(R44)C(O)N(R45)xe2x80x94 or
xe2x80x94N(R46)C(O)C(R47)(R48)xe2x80x94;
X4 is hydrogen, halogen or OR19;
X5 is hydrogen or halogen;
R, R64, R69 and R77 are each independently hydrogen,
SO2R49 or C1-C4alkyl;
R1 is hydrogen, SO2R50, C(O)R51, amino or C1-C4alkyl optionally substituted with CO2R52 or C(O)R53;
R2, R16, R17, R26, R30, R68, R75, R76, R82 and R88 are each independently hydrogen, C3-C6alkenyl or C1-C4alkyl optionally substituted with CO2R54, morpholine or C(O)R55;
R3, R66, R67, R85 and R89 are each independently hydrogen,
Cl-C4alkyl or NR56R57;
R4, R18 and R19 are each independently hydrogen,
C1-C4alkyl, C1-C4haloalkyl, C(O)R58, C3-C4alkenyl or C3-C4alkynyl;
R56 is SO2R49;
R57 is hydrogen or C1-C4alkyl;
R5 and R72 are each independently NR60R61 or indazole;
R6, R11, R12, R14, R15, R20, R21, R22, R25, R28, R29, R31, R32, R33, R35, R45, R46 and R80 are each independently hydrogen or methyl;
R7 is C1-C4alkyl optionally substituted with cyano or C(O)R62;
R8 is hydrogen or C1-C4alkoxy;
R9 and R90 are each independently C1-C4alkyl;
R10 is hydrogen or C1-C3alkyl;
R13, R24 and R36 are each independently hydrogen or chlorine;
R23 is NR63R64;
R34 is C1-C3haloalkyl;
R37 is C2-C4alkoxyalkyl;
R38 and R39 are each independently C1-C3haloalkyl, C1-C3alkyl or propargyl;
R40, R41 and R42 are each independently hydrogen, C(O)R66, C(S)R67, CO2R68, C(xe2x95x90NOR69),
C1-C3alkyl optionally substituted with any combination of one or two halogen atoms, one or two C1-C3alkoxy groups, one or two C1-C3haloalkoxy groups, one SO2R72 group, one or two cyano groups, one C3-C5cycloalkyl group, one OSO2R73 group, one C(O)R74 group, one CO2R75 group, one C(O)SR76 group, one C(O)NR77R78 group, one to two OR79 groups, one P(O)(OR80)2 group, one 1,3-dioxolane group or one 1,3-dioxane group, or
phenyl optionally substituted with any combination of one halogen atom, one or two methyl groups, one methoxy group, one halomethyl group or one OR83 group;
R43, R44, R47 and R48 are each independently hydrogen or methyl, or R43 and R44 or R47 and R48 may be taken together with the atom to which they are attached to form a cyclopropyl group;
R49, R50 and R86 are each independently Cl-C4alkyl or NR93R94;
R51, R52, R53, R54, R55, R58, R60, R61, R62, R73, R74, R78 and R87 are
each independently hydrogen, C1-C4alkyl or C1-C4haloalkyl;
R79 and R83 are each independently hydrogen, C(O)R85,
SO2R86, C1-C4haloalkyl, C3-C4alkenyl or
C1-C3alkyl substituted with one OC(O)R87, CO2R88, C(O)R89, C(OR90)2 or cyano group;
R93 and R94 are each independently hydrogen or C1-C8alkyl; and
p is 0, 1 or 2.
The process of the present invention is especially useful for the preparation of 6-(trifluoromethyl)uracil compounds having the structural formula IX 
wherein
Z3 is hydrogen or methyl;
X5 is hydrogen or halogen;
R40 is hydrogen, C(O)R66, C(S)R67, CO2R68,
C1-C3alkyl optionally substituted with any combination of one or two halogen atoms, one or two C1-C3alkoxy groups, one or two C1-C3haloalkoxy groups, one SO2R72 group, one or two cyano groups, one C3-C5cycloalkyl group, one OSO2R73 group, one or two OR79 groups, one P(O)(OR80)2 group, one 1,3-dioxolane group or one 1,3-dioxane group, or
phenyl optionally substituted with any combination of one halogen atom, one or two methyl groups, one methoxy group, one halomethyl group or one OR83 group;
R66, R67, R85 and R89 are each independently hydrogen,
C1-C4alkyl or NR56R57;
R56 is SO2R49;
R57 is hydrogen or C1-C4akyl;
R49 and R86 are each independently C1-C4alkyl or NR93R94;
R93 and R94 are each independently hydrogen or C1-C8alkyl;
R68 and R88 are each independently hydrogen, C3-C6alkenyl or C1-C4alkyl optionally substituted with CO2R54, morpholine or C(O)R55;
R54, R55, R60, R61, R73 and R87 are each independently hydrogen, C1-C4alkyl or C1-C4haloalkyl;
R72 is NR60R61 or indazole;
R79 and R83 are each independently hydrogen C(O)R85, SO2R86,
C1-C4haloalkyl, C3-C4alkenyl or
C1-C3alkyl substituted with one OC(O)R87, CO2R88, C(O)R89, C(OR90)2 or cyano group;
R80 is hydrogen or methyl; and
R90 is C1-C4alkyl.
Exemplary of halogen hereinabove are fluorine, chlorine, bromine and iodine. The terms xe2x80x9chalomethylxe2x80x9d, xe2x80x9cC1-C4haloalkylxe2x80x9d, xe2x80x9cC1-C8haloalkylxe2x80x9d, xe2x80x9cC1-C3haloalkoxyxe2x80x9d, xe2x80x9cC1-C4haloalkoxyxe2x80x9d and xe2x80x9cC1-C8haloalkoxymethylxe2x80x9d are defined as a methyl, C1-C4alkyl, C1-C8alkyl, C1-C3alkoxy, C1-C4alkoxy or C1-C8alkoxymethyl group substituted with one or more halogen atoms. In formula V above, alkali metals include sodium, potassium and lithium, and alkaline earth metals include calcium and magnesium. Organic ammonium cations suitable for use in the present invention include, but are not limited to, a group consisting of a positively charged nitrogen atom joined to from one to four aliphatic groups, each containing from one to sixteen carbon atoms.
In formula V above, 5- to 12-membered monocyclic or fused bicyclic, heterocyclic rings include, but are not limited to, benzimidazole, imidazole, imidazoline-2-thione, indole, isatoic anhydride, morpholine, piperazine, piperidine, purine, pyrazole, pyrrole, pyrrolidine and 1,2,4-triazole rings wherein each ring is optionally substituted with one or more groups independently selected from halogen, cyano, nitro, amino, hydroxyl, C1-C4alkyl, C1-C4haloalkyl, C1-C4alkoxy, C1-C4haloalkoxy, or C1-C4haloalkylsulfonyl groups.
Starting formula II xcex2-amino-xcex2-(perfluoroalkyl)-acrylate compounds are known in the art and may be prepared according to the procedures described in U.S. Pat. No. 5,777,154; Journal of Heterocyclic Chemistry, 9, pages 513-522 (1972); and Institute of Chemistry, Urals Scientific Center, Academy of Sciences of the USSR, Sverdlovsk, pages 1442-1447 (1987)xe2x80x94English translation of Zhurnal Organicheskoi Khimii, 22(8), pages 1603-1609 (1986).
Carbamoyl chloride compounds of formula III are known in the art and may be prepared by conventional procedures. In addition, certain formula III carbamoyl chloride compounds are commercially available.
Amine compounds having the structural formula VIa 
wherein X1, X5 and R40 are as described hereinabove, may be prepared, as shown in Flow Diagram I, by cyclizing a ketone of formula X with sulfur and ammonium hydroxide or ammonia to form a nitrobenzisothiazole of formula XI, and reducing the formula XI compound using conventional reducing agents such as iron in acetic acid. 
Starting amine compounds having the structural formula VIb 
wherein X1, X5 and R41 are as described hereinabove, may be prepared, as illustrated in Flow Diagram II, by reacting a ketone of formula XII with hydroxylamine hydrochloride optionally in the presence of sodium acetate to form an oxime of formula XIII, cyclizing the formula XIII compound with a base such as potassium hydroxide to form a nitrobenzisoxazole of formula XIV, and reducing the formula XIV compound using conventional reducing agents such as tin(II) chloride in acetic acid. 
Alternatively, formula XIV nitrobenzisoxazole compounds may be prepared, as shown in Flow Diagram III, by reacting a ketone of formula XV with hydroxylamine hydrochloride optionally in the presence of a base such as sodium acetate to form an oxime of formula XVI, cyclizing the formula XVI compound with 1,1xe2x80x2-carbonyldiimidazole in the presence of a base such as triethylamine to form a benzisoxazole of formula XVII, and nitrating the formula XVII compound using conventional methods such as a nitric acid/sulfuric acid mixture. 
Intermediate compounds of formulas XI and XIV wherein R40 and R41 are OR43 may be prepared, as shown in Flow Diagram IV, by nitrating a benzisoxazol-3-ol or benzisothiazol-3-ol of formula XVIII with a conventional nitrating agent such as a nitric acid/sulfuric acid mixture to form a 5-nitrobenzisoxazol-3-ol or 5-nitrobenzisothiazol-3-ol of formula XIX, and reacting the formula XIX compound with an electrophile of formula XX in the presence of a base such as potassium carbonate. 
Formula XI and XIV intermediate compounds wherein R40 and R41 are Cl or Br may be prepared, as shown in Flow Diagram V, by reacting a 5-nitrobenzisoxazol-3-ol or 5-nitrobenzisothiazol-3-ol of formula XIX with phosphorous oxychloride, phosphorous oxybromide or phosphorous pentabromide. 
Other methods For the preparation of formula VIa and VIb amine compounds will become apparent from the examples set forth below. In addition, certain compounds of formulas VIa, VIb, XI and XIV may be converted into other compounds of formulas VIa, VIb, XI and XIV by using conventional procedures known to those skilled in the art.
Other formula VI amine compounds are known in the art and may be prepared according to the procedures described in EP 561319-A; EP 540023-A; EP 545206-A; EP 542685-A; EP 473551-A; EP 476697-A; EP 489480-A; EP 496595-A; EP 420194-A; EP 648749-A; EP 705829-A; EP 714602-A; JP 9241245; JP 9301973; U.S. Pat. Nos. 5,169,430; 5,310,723; 5,324,854; 5,391,541; 5,399,543; 5,484,763; 5,523,278; 5,602,077; 5,661,108; WO 93/14073; WO 94/10155; WO 94/24128; WO 91/07393; WO 91/107392; WO 95/04461; WO 95/05079; WO 95/05080; WO 95/17096; WO 95/25725; WO 95/29168; WO 95/32952; WO 95/33746; WO 96/02518; WO 96/08151; WO 96/14315; WO 96/28442; WO 96/34859; WO 96/35679; WO 97/01541; WO 97/01542; WO 97/05118; WO 97/07105; WO 97/08170; WO 97/08171; WO 97/08953; WO 97/12884; WO 97/12886; WO 97/29094; WO 97/29105; WO 97/34484; WO 97/35845; WO 97/42176; WO 97/42188; WO 97/45418; WO 97/47607; WO 98/02422; WO 98/06706; WO 98/08824; WO 98/27057; WO 98/27067; WO 98/27082; and WO 98/27088, among others.
In order to facilitate a further understanding of this invention, the following examples are presented primarily for the purpose of illustrating more specific details thereof. The scope of the invention should not be deemed limited by the examples but encompasses the entire subject matter defined in the claims.